19th Annual Center for Biomedical Neuroscience Retreat

The hypothalamic-pituitary-adrenal (HPA) axis is an important hormonal system in man and rodents, which ultimately controls secretion of glucocorticoids from the adrenal gland: cortisol in humans, and corticosterone in rats. Stress-induced activation of the HPA axis resulting in acute elevations in circulating glucocorticoids levels protect the organism from physiological insult by regulating a variety of physiological processes. For example, they provide adequate substrate for increased metabolic need and help to sustain blood pressure and depress immune function. On the other hand, chronic elevations in glucocorticoids produced by repeated stress exposure have been implicated in the pathogenesis of several forms of systemic, neurodegenerative, and affective disorders.We have evidence showing that testosterone acts centrally to inhibit stress-induced HPA activity and corticosterone release in the rat. Using a functional neuroanatomical approach assisted by tract-tracing, in-situ histochemical, and early-gene techniques, our goal is to reveal the routes, neurotransmitters, and cellular mechanisms by which testosterone alters circuits in the brain conveying stress-related information. Because gonadal steroid release in both males and females varies as a function of reproductive and social status, this research will lay the groundwork for future studies aimed at understanding the central bases of social- and gender-based differences in stress reactivity.